Excitatory mechanism of deflationary slowly adapting pulmonary stretch receptors in the rat lung.

The excitatory responses of deflationary slowly adapting pulmonary stretch receptor (SAR) activity to lung deflation ranging from approximately -15 to -25 cm of H(2)O for approximately 5 s were examined before and after administration of flecainide, a Na(+) channel blocker, and K(+) channel blockers, such as 4-aminopyridine (4-AP) and tetraethylammonium (TEA). The experiments were performed in anesthetized, artificially ventilated rats after unilateral vagotomy. The deflationary SARs increased their activity during lung deflation and its effect became more pronounced by increasing the degree of negative pressure. During lung deflation the average values for the deflationary SAR adaptation index (AI) were below 40%. Intravenous administration of veratridine (50 microg/kg), an Na(+) channel opener, stimulated deflationary SAR activity: one maintained excitatory activity mainly during deflation and the other receptors showed a tonic discharge during both deflation and inflation. Despite the difference in deflationary SAR firing patterns after veratridine administration, flecainide treatment (6.0 mg/kg) blocked veratridine-induced deflationary SAR stimulation and also caused strong inhibition of the excitatory responses of deflationary SARs to lung deflation. Under these conditions, the average values for deflationary SAR AI were over 90%. The responses of deflationary SARs and deflationary SAR AI to lung deflation were not significantly altered by pretreatment with either 4-AP (0.7 and 2.0 mg/kg) or TEA (2.0 and 6.0 mg/kg). These results suggest that the excitatory effect of lung deflation on deflationary SAR activity is mediated by the activation of flecainide-sensitive Na(+) channels on the nerve terminals of deflationary SARs.     

Coronary artery bypass in dextrocardia with situs inversus totalis--a case report

A 71-year-old woman was admitted to our hospital by ambulance, because of right chest pain and hypotension. Chest X-ray and standard 12-lead ECG showed mirror-image dextrocardia with situs inversus totalis. ECG with right-left reversal of all leads showed acute inferior myocardial infarction. The patient underwent coronary bypass surgery due to postinfarction angina, and she is now doing well 2 years following the operation. Mirror-image dextrocardia with situs inversus totalis is very unusual. But the patients are believed to have normal longevity, and presumably have an incidence of atherosclerotic coronary artery disease similar to the general population. To our knowledge, this is the first case of coronary bypass surgery on a patient with mirror-image dextrocardia in Japan.     

Experimental evaluation for tricuspid annular constriction with the model of tricuspid annular dilatation

We have obtained the good result about tricuspid annular constriction (TAC) for secondary tricuspid insufficiency. The purpose of this study is to investigate the effectiveness of TAC for the experimental model of tricuspid annular dilatation. First of all, tricuspid annular dilatation was made surgically in 8 mongrel dogs by placing 8 incisions to tricuspid annulus except septal cusp under the condition of heart-lung preparation. On clinical evaluation, septal annulus was kept to be intact in many cases compared with the two other areas. This experimental model of tricuspid annular dilatation was considered to be substituted to the clinical model of tricuspid annular dilatation. TAC suture was surrounded circumferentially around the dilated tricuspid annulus. And then, TAC suture was pulled out from the right atrial wall, and the circumferential length of tricuspid annulus was completely accommodated by pulling the TAC suture. The hemodynamic status was observed by right atrial pressure (V wave and mean) and right ventricular end-diastolic pressure (RVEDP). After heart resuscitation and gradual increase of preload, right atrial pressure was significantly elevated especially right atrial pressure (V wave) compared with control values. When 2 cm of circumferential length of tricuspid annulus on an average was constricted by shortening of TAC suture, right atrial pressure was significantly decreased, and then RVEDP tended to decrease. It was shown that TAC was an effective operative technique for the secondary tricuspid annular dilatation and tricuspid insufficiency from the standpoint of experimental aspect as well as clinical results.     

A case of congenital antithrombin II deficiency with pulmonary infarction

A 48-year-old woman was admitted because of increased bloody sputum. Since she had had a history of repeated thrombotic episodes including venous thrombosis in the lower limbs (21 year old) and pulmonary emboli developing into pulmonary infarction (41 years old), the patient was treated with anti-coagulant therapy using Warfarin for 7 years. Warfarin was discontinued after admission and heparin was administered instead at a relatively low dose of 5,000 units daily, resulting in a considerable diminution of hemoptysis. Unfortunately however, it caused a relapse of active thrombosis associated not only with a significant increase of the product of fibrinolysis (FDP), LDH and GOT but with a concomitant decrease of the platelet count. Hematological examinations concerning coagulation and fibrinolysis remained within a normal range except for the serum concentration of antithrombin III (AT III) and its functional property with regard to the heparin cofactor, which were 8.8 mg/dl and 48%, respectively. Since the findings were consistent with congenital deficiency of AT III, some members of her family were also examined. The concentration of AT III and its activity in the patient's son and her daughter deteriorated in a similar manner, indicating that this was a definite case of congenital deficiency of AT III. The clinical manifestations of 87 cases with congenital AT III deficiency, belonging to 24 families reported in Japan were reviewed.     

High human IgG levels in severe combined immunodeficient mouse reconstituted with human splenic tissues from patients with gastric cancer.

We implanted normal peripheral blood lymphocytes (PBL) from healthy donors and splenic tissues from patients with gastric cancers into the severe combined immunodeficient (SCID) mouse, demonstrating that SCID mouse with splenic tissue can produce a high level of human immunoglobulin G (IgG). The normal PBLs at 10(7) and 10(8)/mouse were implanted intraperitoneally, and three splenic tissues with a size of 3 x 3 x 3 mm from gastric cancer patients were inoculated subcutaneously into the bilateral backs of the mice. At 2, 4, 6 and 8 weeks after inoculation, mice were killed, and the human IgG was assessed by an ELISA method. SCID mice with splenic tissue revealed high human IgG levels from 2 weeks after inoculation and approximately 2 mg of IgG per ml was observed at 8 weeks post-implantation, while the IgG levels in mice treated with PBLs were limited. Since the half life of the extrinsic human IgG was 10.2 days, the high level of human IgG in the SCID mice was supposed to be produced by human plasma cells in the splenic tissue from gastric cancer patients. This model was thought to be adequate for evaluating human immunological functions in vivo.     

Subclinical gallbladder carcinoma.

Clinicopathologic features of 31 patients with subclinical gallbladder carcinoma were reviewed in an attempt to determine the parameters for a course of therapy. Subclinical gallbladder carcinoma was defined as a gallbladder carcinoma that was first diagnosed microscopically by surgical pathologists. Of 31 patients, there were 26 women and 5 men, ranging in age from 54 to 84 years (mean age: 68 years). All 31 patients had undergone cholecystectomy for presumed benign gallbladder conditions. The 31 gallbladder carcinomas consisted of 6 carcinomas limited to the mucosa or the muscle coat (m or pm) and 25 carcinomas extending into the subserosal layer with surgical margins free of malignant cells in 14 (ss ew [-]) and affected by malignant cells in 11 (ss ew [+]). Cumulative 1-year, 3-year, and 5-year survival rates of six patients with m or pm carcinoma were 100% (p less than 0.001, versus ss ew [+] at 1 year), 100% (p less than 0.05, versus ss ew [-] at 3 years), and 100% (p less than 0.05, versus ss ew [-] at 5 years) compared with 91% (p less than 0.01, versus ss ew [+] at 1 year), 65%, and 65% of 14 with ss ew (-) carcinoma and 43%, 0%, and 0% of 11 with ss ew (+) carcinoma. Thirteen of the 31 patients died of local recurrence and/or liver metastasis. Univariate logrank analysis of 10 prognostic factors showed that depth of invasion, venous invasion, and surgical margin were prognostic factors. Multivariate Cox-regression analysis of these three profound factors demonstrated that surgical margin and depth of invasion were independent variables. These results showed that m or pm subclinical gallbladder carcinoma does not necessarily require an additional operation, whereas ss ew (-) and ss ew (+) carcinomas necessitate additional resection and adjuvant treatment.     

Effect of fenbufen on the pharmacokinetics of sparfloxacin in rats.

The effects of fenbufen on the serum concentrations and penetration into the brain and CSF of sparfloxacin (AT-4140), a new quinolone antibacterial agent, were investigated in rats. At designated times after a bolus iv dose of sparfloxacin 10 mg/kg with or without fenbufen 20 mg/kg, arterial blood, CSF and whole brain were simultaneously collected from each rat. Sparfloxacin concentrations were assayed by HPLC. Serum concentration of sparfloxacin declined bi-exponentially with time and was not changed by coadministered fenbufen. Binding sparfloxacin to serum protein slightly decreased after the coadministration. No elevation of sparfloxacin concentrations was observed in either brain or CSF after coadministration with fenbufen except for only a few time-points. The pharmacokinetic analysis based on the physiological model indicated that fenbufen did not affect the permeability across the blood-brain or blood-CSF barrier. These results suggest that fenbufen may be unlikely to affect the pharmacokinetics, involving the entry into the central nervous system, of sparfloxacin.     

β2-glycoprotein I, anti-β2-glycoprotein I, and fibrinolysis

β₂-glycoprotein-I (β₂GPI) is a phospholipid-binding plasma protein that consists of five homologous domains. Domain V is distinguished from others by bearing a positively charged lysine cluster and hydrophobic extra C-terminal loop. β₂GPI has been known as a natural anticoagulant regulator. β₂GPI exerts anticoagulant activity by inhibition of phospholipid-dependent coagulation reactions such as prothrombinase, tenase, and factor XII activation. It also binds factor XI and inhibits its activation. On the other hand, β₂GPI inhibits anticoagulant activity of activated protein C. According to the data from knockout mice, β₂GPI may contribute to thrombin generation in vivo. Phospholipid-bound β₂GPI is one of the major target antigens for antiphospholipid antibodies present in patients with antiphospholipid syndrome (APS). Binding of pathogenic anti-β₂GPI antibodies increases the affinity of β₂GPI to the cell surface and disrupts the coagulation/fibrinolysis balance on the cell surface. These pathogenic antibodies activate endothelial cells via signal transduction events in the presence of β₂GPI. Impaired fibrinolysis has been reported in patients with APS. Using a newly developed chromogenic assay, we demonstrated lower activity of intrinsic fibrinolysis in euglobulin fractions from APS patients. Addition of monoclonal anti-β₂GPI antibodies with β₂GPI also decreased fibrinolytic activity in this assay system. β₂GPI is proteolytically cleaved by plasmin in domain V (nicked β₂GPI) and becomes unable to bind to phospholipids, reducing antigenicity against antiphospholipid antibodies. This cleavage occurs in patients with increased fibrinolysis turnover. Nicked β₂GPI binds to plasminogen and suppresses plasmin generation in the presence of fibrin, plasminogen, and tissue plasminogen activator (tPA). Thus, nicked β₂GPI plays a role in the extrinsic fibrinolysis via a negative feedback pathway loop.     

Anti-Candida albicans activity of essential oils including Lemongrass (Cymbopogon citratus) oil and its component, citral]

The effects of 12 essential oils, popularly used as antifungal treatments in aromatherapy, on growth of Candida albicans were investigated. Mycelial growth of C. albicans, which is known to give the fungus the capacity to invade mucosal tissues, was inhibited in the medium containing 100 micro g/ml of the oils: lemongrass (Cymbopogon citratus), thyme (Thymus vulgaris), patchouli (Pogostemon cablin) and cedarwood (Cedrus atlantica). Not only lemongrass oil but also citral, a major component of lemongrass oil (80%), in the range of 25 and 200 micro g/ml inhibited the mycelial growth but allowed yeast-form growth. More than 200 micro g/ml of citral clearly inhibited both mycelial and yeast-form growth of C. albicans. These results provide experimental evidence suggesting the potential value of lemongrass oil for the treatment of oral or vaginal candidiasis.